Severe COVID-19 and related hyperferritinaemia: more than an innocent bystander?

The catastrophic outbreak of acute respiratory distress syndrome induced by SARS-CoV-2 (the coronavirus disease 2019, COVID-19) has strongly confirmed the important role of systemic hyperinflammation, independently of the trigger, as a major cause of death. In fact, accumulating evidence suggests that a subgroup of patients with severe COVID-19 is burdened by a cytokine storm syndrome, an overwhelming systemic inflammation with a massive release of pro-inflammatory cytokines. As reported in 150 patients in Wuhan, China, a subset of patients with COVID-19 are characterised by raised levels of ferritin, which identified those patients at higher risk of poor outcome (1297.6 ng/mL in non-survivors compared with 614.0 ng/mL in survivors). Although the amplitude of ferritin elevation is not comparable, this finding may resemble what is observed in diseases included under the umbrella of the hyperferritinaemic syndrome.2 This syndrome includes macrophage activation syndrome (MAS), systemic juvenile idiopathic arthritis, adult-onset Still’s disease (AOSD) and catastrophic anti-phospholipid syndrome, which are burdened by severe clinical picture and high mortality rate.2 Ferritin, the common denominator of all these diseases, is an iron storage protein comprising 24 subunits of two types, heavy (FeH) and light (FeL) subunits, differently expressed in tissues. Read more....